The S100P protein is a member of the family of calcium binding proteins called S100 (Zhang H. et al. 2003. J Mol Biol, 325:785-794) which presents high expression levels in a wide variety of different tumor types. Encompassing all of tumor development, its activity is mainly associated with the establishment of tumor cell resistance to chemotherapy treatments (Bertram J. et al. 1998. Anticancer Drugs, 9:311-317), an increase of the proliferative and invasive capacity for the tumor cell and a greater metastatic capacity. Accordingly, there is a correlation between high expression levels of S100P in a tumor and a low life expectancy in patients with cancer.
The gene encoding the S100P protein is expressed in several forms of the disease, including pancreatic cancer (Logsdon C. D. et al. 2003. Cancer Res, 63:2649-2657), breast cancer (Guerreiro Da Silva I.D. et al. 2000. Int J Oncol, 16:231-240; Wang G. et al. 2006. Cancer Res, 66:1199-1207), colon cancer (Fuentes M. K. et al. 2007. Dis Colon Rectum, 50:1230-1240), prostate cancer (Mousses S. at al. 2002. Cancer Res, 62:1256-1260), lung cancer (Diederichs S. et al. 2004. Cancer Res, 64:5564-5569) and ovarian cancer (Surowiak P. et al. 2007. Histopathology, 51:125-128), among others. The S100P protein has intra- and extracellular function and, specifically, at the extracellular level, secreted by the tumor cell, it is known to have an autocrine interaction with the RAGE receptor present in the tumor cell membrane, activating the aforementioned mechanism (Arumugam T. et al. 2004. J Biol Chem, 279:5059-5065).
Several studies have confirmed the benefits of blocking S100P/RAGE in tumor cells by developing peptide antagonists of S100P and small molecules such as cromolyn (Arumugam T. and Logsdon C. D. 2010. Amino acids).
Therefore, there is a need in the state of the art to provide new therapeutic approaches for the treatment of cancer targeting the S100P protein.
In addition, at a diagnostic level, S100P can be considered a good marker in the differentiation process of a normal cell towards a tumor cell, and therefore it is a good biomarker in the cytological examination of tumors. In this regard, anti-S100P monoclonal antibodies potentially useful for the immunohistochemical detection of the expression of S100P in cancerous tissue are known (Parkkila S. et al. 2008. BMC Clinical Pathology, 8:2). This type of analysis presents the drawback of requiring a patient biopsy. Therefore, there is a need in the state of the art to provide a simpler and less invasive method for the clinical diagnosis of cancer by means of detecting the levels of S100P in a subject.